Lipid metabolism Flashcards
triglycerides
-triglycerides are storage molecules for lipids
-water insoluble
- no risk of undesired breakage
triglyceride transport
- ingested triglycerides need a protein carrier to travel through the blood, to make them overall water soluble
triglyceride breakdown
- uses coenzyme A to breakdown triglycerides to be used for fuel
- beta-oxidation
how are fatty acid fuels obtained (3 ways)
- fats consumed in diet
- fats stored in cells as lipid droplets
- synthesis of fats by the liver
bile salts definition
- synthesized molecules from cholesterol in the liver, stored in the gallbladder, and released into the small intestine after ingestion of fatty meal
bile salts role in triglyceride breakdown
- solubilizes triglycerides by creating a mixed micelle of bile salts and triacylglycerol (aka triglyceride)
- aids in lipid breakdown/ and absorption of digested products
what happens after bile salts interaction?
- micelle is able to interact with water-soluble pancreatic lipase in the intestine
- which breaks triglycerides to smaller pieces (mono/diglycerides, free FA)
- these products dissolve into intestinal mucosa and are then reconverted into triacylglycerol packaged into chylomicrons in the ER
chylomicron structure
- triacylglycerol in the center, with protein, phospholipids and cholesterol on the outside
what is an apolipoprotein
lipid-binding protein in the blood
what is a lipoprotein
combination of a lipid and an apolipoprotein
what is a chylomicron
- largest type of lipoprotein and least dense
- it’s synthesized in the epithelial cells of the small intestine, and transported via lymphatic tissue into the bloodstream
- delivers dietary triglycerides to various tissue
what important apolipoprotein does chylomicrons contain and what do they do?
ApoC-II, important because it activate lipoprotein lipase which allows triglycerides to breakdown into FA’s in tissues
what happens to chylomicron remnants after chylomicrons are broken down?
Re-circulated into the liver, cholesterol is released and remainder is degraded into lysosomes in the hepatocytes
VLDL (very low-density lipoproteins)
- happens when intake of FA’s is more than what’s need immediately for fuel:
- then is converted to triacylglycerol in the liver and packaged as VLDL
- transported to muscle for energy or adipose tissue for storage of lipid droplets
LPL (lipoprotein lipase)
enzyme that breaks down chylomicrons and VLDL from triglycerides to FA’s, different function based on tissue
- cardiac and skeletal muscle: provides energy
- adipose tissue: stimulates triacylglycerol storage
LPL in high vs low insulin levels
- high insulin: increase of LPL in adipose tissue = fuel storage
- low insulin: increase LPL activity in muscle tissue, release FA’s from VLDL for fuel
IDL (intermediate-density lipoprotein)
- these are equivalent to VLDL remnants
- either are removed from the bloodstream by the liver or a precursor for LDL’s
LDL (low-density lipoproteins)
-uses apolipoprotein ApoB-100 to transport to target tissue
- transports cholesterol to tissues, cholesterol uptake into extrahepatic tissues
HDL (high-density lipoprotein)
- contains enzyme cholesterol acyl transferase (LCAT)
- catalyzes the formation of cholesteryl esters
- extract cholesterol from chylomicrons and VLDL remnants
why is HDL transportation unique
it’s reversal cholesterol transport, which means it picks up cholesterol in the tissues and carries it to the liver
what organ is capable of disposing of significant amounts of cholesterol
the liver
Acyl-CoA: cholesterol acyltransferase (ACAT)
esterifies free cholesterol by linking it to a fatty acid, preparing it for storage in liver cells or packaging into lipoproteins
LDL - lipid transport
- distribution and delivery of cholesterol to peripheral tissues is mediated by binding of LDL to LDL receptors on plasma membrane of target cells
LDL receptors relation to high intracellular cholesterol
- high intracellular cholesterol reduces LDL receptors and therefore reduces its own synthesis by inhibiting enzymes HMG-CoA reductase/synthase
LDL receptors relation to high LDL
- high LDL in the plasma correlates to atherosclerosis, because it saturates LDL receptors. Then, it enters via a nonspecific endocytic process leading to excessive cholesterol uptake
what does “bulk-phase pinocytosis” refer to?
unregulated uptake of cholesterol because of excess LDL
Beta-oxidation pathway
series of enzyme catalyzed rxns that degrade FA’s by removing 2-carbon units from the carboxyl end
- takes place in the mito matrix
1st part of Beta-oxidation pathway
free FA’s need to be activated, which occurs by the enzyme fatty acyl-CoA synthetase. Turns free FA’s into fatty acyl-CoA
- occurs in the cytoplasm, requires ATP
beta-oxidation pathway if FA chain is large
fatty acyl-CoA changes carriers from CoA to carnitine in the IMS, so that it can move into the mito matrix.
- changes back to CoA in the mito matrix
beta-oxidation overview
highly exergonic, purpose it to generate energy through the break down of FA’s, needs 2 ATP
results in:
- 1 NADH
- 1 FADH2
- 1 acetyl-CoA and 1 fatty acyl-CoA
what can the product of beta-oxidation (acetyl-CoA) be used for?
the citric acid cycle or becomes a ketone body
ketone bodies use
important metabolic fuel for many peripheral tissues
- such as, heart and skeletal muscle, or the brain (uses ketone bodies as fuel in starvation)
ketosis
a condition in which ketone bodies are produced faster than metabolized, leads to ketoacidosis (lowered blood pH)
FA biosynthesis
- occurs through condensation of C2 units, opposite of beta-oxidation (different pathway though)
- mainly in the liver and adipose tissue
- takes place in cytoplasm, endergonic process
requirements for FA biosnythesis
each round requires:
- an activated malonyl-CoA (1 ATP per round for activation)
- 2 NADPH
regulation of FA metabolism
- glucagon, epinephrine, and norepinephrine stimulate cAMP, which stimulates PKA (phosphorylation)= active beta-oxidation and inhibited FA biosynthesis
- insulin decreases cAMP, activates acetyl-CoA carboxylase (dephosphorylation) = active FA biosynthesis, inhibits beta-oxidation
AMPK on FA metabolism
- activated by AMP and inhibited by ATP
- promotes catabolic process and inhibits anabolic ones (so activates glycolysis and FA oxidation, inhibits FA synthesis)
